Novel process for the preparation of a synthetic intermediate for pesticides

ABSTRACT

Process for the preparation of a compound of general formula (I):  
                 
in which X represents a halogen atom, 
 
by reaction of para-trifluoromethylaniline of formula (II):  
                 
 
with a dihalogen X 2 , 
the two compounds being introduced simultaneously into a polar aprotic solvent in a dihalogen/compound (II) molar ratio ranging from 1.9 to 2.5 and at a temperature ranging from 100 to 300° C.

The present invention relates to a novel process for the preparation ofa 2,6-dihalo-para-trifluoromethylaniline frompara-trifluoromethylaniline.

Numerous studies have already been carried out with the aim ofdeveloping processes for the preparation of2,6-dihalo-para-trifluoromethylanilines. Patent Application WO 00/35851discloses a process for the preparation of a2,6-dihalo-para-trifluoromethylaniline from atrihalo-para-trifluoromethylbenzene at a temperature of between 130 and350° C. in a preferably polar solvent. The use ofpara-trifluoromethylaniline for the preparation of2,6-dihalo-para-trifluoromethylaniline does not appear in this patentapplication.

Patent Applications FR 2 810 665 and WO 01/64623 disclose a process forthe preparation of 2,6-dichloro-para-trifluoromethylaniline bychlorination of precursor anilines in a hydrofluoric acid medium. Theprecursor compound is trifluoromethylphenylcarbamoyl fluoride. The useof an other solvent than hydrofluoric acid is not mentioned.

Nevertheless, these processes result in the formation of impurities,such as polycondensates or heavy polychlorinated compounds, which makeit impossible to use 2,6-dihalo-para-trifluoromethylaniline in thecontinuation of the preparation of pesticidal compounds ofphenylpyrazole type without subjecting it to a prior purification stage.This purification stage constitutes a major disadvantage when it is amatter of preparing 2,6-dichloro-para-trifluoromethylaniline on anindustrial scale, in particular for the production of pesticides ofphenylpyrazole type.

It has now been discovered, in an entirely surprising way, that theprocess for the preparation of 2,6-dihalo-para-trifluoromethylanilineaccording to the present invention results in a compound which issufficiently pure to be used directly in the continuation of the processfor the production of pesticidal compounds of phenylpyrazole type.

A subject-matter of the present invention is thus a process for thepreparation of a compound of general formula (I):

in which X represents a halogen atom,by reaction of para-trifluoromethylaniline of formula (II):

with a dihalogen X₂,the two compounds being introduced simultaneously into a polar aproticsolvent at a temperature ranging from 100 to 300° C. and at adihalogen/compound (II) molar ratio ranging from 1.9 to 2.5.

In the context of the present invention, X represents a halogen atom. Xcan be a chlorine atom, a bromine atom, an iodine atom or a fluorineatom.

The compound of general formula (I) preferably prepared by virtue of theprocess according to the present invention is2,6-dichloro-para-trifluoromethylaniline, which is particularly usefulin the synthesis of fipronil, an insecticidal compound of phenylpyrazoletype.

The solvent used during the preparation of the compound of generalformula (I) according to the present invention is a polar aproticsolvent. A preferred polar aprotic solvent can be a chlorinated aromaticsolvent, such as monochlorobenzene, or a chlorinated aliphatic solvent,such as dichloroethane. In an entirely preferred way, monochlorobenzenewill be chosen as solvent.

The dihalogen/compound (II) molar ratio is chosen as ranging from 1.9 to2.5 during the preparation of the 2,6-dihalo-para-trifluoromethylanilineaccording to the present invention. The dihalogen/compound (II) molarratio is preferably chosen as ranging from 2 to 2.05.

The temperature of the reaction medium according to the presentinvention is chosen as ranging from 100 to 300° C. The temperature ofthe reaction medium is preferably chosen as ranging from 100 to 130° C.In an entirely preferred way, the temperature of the reaction medium ischosen as ranging from 105° C. to 115° C.

In an entirely preferred way, the process according to the presentinvention consists in preparing 2,6-dichloro-para-trifluoromethylanilineby simultaneously introducing para-trifluoromethylaniline and Cl₂ intomonochlorobenzene in a Cl₂/para-trifluoromethylaniline molar ratio ofbetween 1.85 and 2.05, at a temperature ranging from 105 to 115° C.

The process according to the present invention can be carried outaccording to general techniques known to a person skilled in the art.Thus, the process according to the present invention can be carried outin a jacketed reactor equipped with a stirring device and surmounted bya reflux condenser maintained at a temperature of less than or equal to−10° C. The halogen necessary for the reaction will be introduced via adip pipe arriving with stirring. The stirrer preferably used will makeit possible to provide optimum micromixing of the reactants. This can becarried out by a stirrer of impeller type or by any other stirrer wellknown to a person skilled in the art.

During the reaction according to the present invention, hydrochloricacid in the gaseous form is produced. The latter is subsequentlygenerally absorbed by a sodium hydroxide trap. Aspara-trifluoromethylaniline reacts instantaneously on contact withhydrochloric acid to form para-trifluoromethylaniline hydrochloride,para-trifluoromethylaniline will preferably be fed to the reactor via adip pipe, in order to avoid blockages.

During the introduction of the reactants, a marked tendency to foam issometimes observed. This can generally be avoided by reducing the flowrate for the introduction of the reactants. Nevertheless, in order toavoid the accumulation of foam, the latter should be taken up by theliquid. One answer is therefore generally to increase the stirring rate.

The product obtained by virtue of the process according to the presentinvention (2,6-dihalo-para-trifluoromethylaniline) has a sufficientdegree of purity to be reused directly in the synthesis of thepesticidal compounds of phenylpyrazole type. It is generally consideredthat the degree of purity should be at least 96% in order for theproduct to be able to be used in the continuation of a preparationprocess.

The 2,6-dihalo-para-trifluoromethylaniline obtained can also beisolated, in particular in order to be stored, by distillation of thesolvent according to techniques known to a person skilled in the art.

The example of the preparation of compounds which follows is mentionedwith the aim of illustrating the invention but should on no account beregarded as limiting the latter.

Preparation of 98% 2,6-dichloro-para-trifluoromethylaniline

12 140 kg of pure monochlorobenzene are charged to a 20 m³ jacketedreactor rendered inert with nitrogen. The solvent heel is subsequentlybrought to 110° C. by heating the jacket.

The reactor is subsequently fed with a 70% solution ofpara-trifluoromethylaniline in monochlorobenzene at a flow rate of 792kg/h for 6 h 30 and with Cl₂ at a flow rate of 488 kg/h. The temperatureis maintained at 110° C. by cooling the jacket.

Once feeding is complete, the residual content ofpara-trifluoromethylaniline or of monochloro derivative is monitored. Ifone of these compounds remains, it is then advisable to adjust theamount of chlorine in order to consume the residual product.

At the end of the reaction, the monochlorobenzene is distilled off byplacing the reactor under gradually increasing vacuum through adistillation column. After removal of the solvent, the2,6-dichloro-para-trifluoromethylaniline is cooled to 60° C. beforeemptying the reactor to the storage tank.

The product obtained according to the process described above wasanalysed. The results given in the table below correspond to the mean ofthe analytical results which are obtained for the product over a periodof one year: Monochloro-para- DCpTFMA assay p-TFMA assaytrifluoromethylaniline (solvent-free) (solvent-free) assay 98.1% 0.05%0.09%

These results thus show that the2,6-dichloro-para-trifluoromethylaniline obtained by the processaccording to the present invention is pure to greater than 98%, that thereaction yield is very good, since only 0.05% of reactant (p-TFMA)remains, and that only 0.09% of themonochloro-para-trifluoromethylaniline has not been converted to2,6-dichloro-para-trifluoromethylaniline.

1. Process for the preparation of a compound of general formula (I):

in which X represents a halogen atom, by reaction ofpara-trifluoromethylaniline of formula (II):

with a dihalogen X₂, the two compounds being introduced simultaneouslyinto a polar aprotic solvent in a dihalogen/compound (II) molar ratioranging from 1.9 to 2.5 and at a temperature ranging from 100 to 300° C.2. Process according to claim 1, characterised in that the compound offormula (I) is 2,6-dichloro-para-trifluoromethylaniline.
 3. Processaccording to claim 1, wherein the solvent used is a chlorinatedaliphatic solvent.
 4. Process according to claim 3, characterised inthat the solvent used is dichloroethane.
 5. Process according to claim1, wherein the solvent used is a chlorinated aromatic solvent. 6.Process according to claim 5, characterised in that the solvent used ismonochlorobenzene.
 7. Process according to claim 1, wherein, thereactants are introduced in a dihalogen/compound (II) molar ratioranging from 2 to 2.05.
 8. Process according to claim 1, wherein thetemperature of the reaction medium is chosen as ranging from 100 to 130°C.
 9. Process according to claim 8, characterised in that thetemperature of the reaction medium is chosen as ranging from 105 to 115°C.
 10. Process according to claim 2, characterized in that the reactantsare introduced into monochlorobenzene in a dichlorine/compound (II)molar ratio ranging from 1.85 to 2.05, at a temperature ranging from 105to 115° C.
 11. Process according to claim 2, wherein the solvent used isa chlorinated aliphatic solvent.
 12. Process according to claim 2,wherein the solvent used is a chlorinated aromatic solvent.